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Specific interaction of hepatitis C virus glycoproteins with mannan binding lectin inhibits virus entry

Protein & Cell 2010年第7期1卷 664-674页

作者： Kristelle S.Brown Michael J.Keogh Ania M.Owsianka Richard Adair Arvind H.Patel James N.Arnold Jonathan K.Ball Robert B.Sim alexander w.tarr Timothy P.Hickling Institute of Infection Immunity and InflammationSchool of Molecular Medical SciencesThe University of NottinghamQueen’s Medical CentreNottinghamNG72UHUK The Medical Research Council-University of Glasgow Centre for Virus Research University of GlasgowChurch StreetGlasgowG115JRUK MRC Immunochemistry Unit Department of BiochemistryUniversity of OxfordOX13QUUK Present address:Vitrology Biotech 5 South AvenueClydebank Business ParkGlasgowG812LGUK Present address:Pfizer Technologies Ltd. Ramsgate RoadSandwichKentCT139NJUK

Mannan-binding lectin(MBL)is a soluble innate immune protein that binds to glycosylated *** acts as an opsonin and activates complement,contributing to the destruction and clearance of infecting *** C virus(HCV)encodes two envelope glycoproteins E1 and E2,expressed as non-covalent E1/E2 heterodimers in the viral envelope.E1 and E2 are potential ligands for *** we describe an analysis of the interaction between HCV and MBL using recombinant soluble E2 ectodomain fragment,the full-length E1/E2 heterodimer,expressed in vitro,and assess the effect of this interaction on virus entry.A binding assay using antibody capture of full length E1/E2 heterodimers was used to demonstrate calcium dependent,saturating binding of MBL to HCV *** with various saccharides further confirmed that the interaction was via the lectin domain of *** binds to E1/E2 representing a broad range of virus *** was shown to neutralize the entry into Huh-7 cells of HCV pseudoparticles(HCVpp)bearing E1/E2 from a wide range of *** were neutralized to varying *** was also shown to neutralize an authentic cell culture infectious virus,strain JFH-1(HCVcc).Furthermore,binding of MBL to E1/E2 was able to activate the complement system via MBL-associated serine protease *** conclusion,MBL interacts directly with HCV glycoproteins,which are present on the surface of the virion,resulting in neutralization of HCV particles.

关键词： hepatitis C virus neutralization mannose binding lectin chronic viral infection

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Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng Thomas Skutella Karl Kiening Andreas Unterberg alexander Younsi Department of Neurosurgery Heidelberg University HospitalHeidelbergGermany Department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera alexander J.P.Goldschmidt Damien D.Pearse w.Dalton Dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Varicocele and testicular function

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Asian Journal of Andrology 2015年第4期17卷 659-667页

作者： alexander w Pastuszak Center for Reproductive Medicine Baylor College of Medicine Houston TX USA Scott Department of Urology Bay or Co ege of Medicine Houston TX USA Divisionof Urology University of Texas Med ca School at Houston Houston TX USA Department of Urology University of Texas MD Anderson Cancer Center HoustonTX USA

Testicular varicocele, a dilation of the veins of the pampiniform plexus thought to increase testicular temperature via venous congestion, is commonly associated with male infertility. Significant study has clarified the negative impact of varicocele on semen parameters and more recent work has shed light on its detrimental effects on the molecular and ultrastructural features of sperm and the testicular microenvironment, as well as more clearly defined the positive impacts of treatment on couples＇ fertility. The relationship between varicocele and testicular endocrine function, while known for some time based on histologic evaluation, has become more apparent in the clinical setting with a growing link between varicocele and hypogonadism. Finally, in the pediatric setting, while future study will clarify the impact of varicocele on fertility and testicular function, recent work supports a parallel effect of varicocele in adolescents and adults, suggesting a re-evaluation of current treatment approaches in light of the progressive nature of the condition and potential increased risk of future disease.

关键词： hypogonadism Leydig cell male fertility oxidative stress Sertoli cell ultramorphology varicocele

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Genome-wide association studies for inflorescence type and remontancy in Hydrangea macrophylla

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Horticulture Research 2020年第1期7卷 2477-2485页

作者： Xingbo wu Lisa w.alexander Oak Ridge Institute of Science and Technology Otis L.Floyd Nursery Research Center472 Cadillac LaneMcMinnvilleTNUSA U.S.Department of Agriculture Agricultural Research ServiceU.S.National ArboretumFloral and Nursery Plants Research UnitOtis L.Floyd Nursery Research Center472 Cadillac LaneMcMinnvilleTNUSA

Inflorescence type and remontancy are two valuable traits in bigleaf hydrangea(Hydrangea macrophylla L.)and both are recessively *** marker-assisted selection(MAS)can greatly reduce the time necessary to breed cultivars with desired *** this study,a genome-wide association study(GwAS)using 5803 single-nucleotide polymorphisms(SNPs)was performed using a panel of 82 bigleaf hydrangea *** SNP locus(Hy_CAPS_Inflo)associated with inflorescence type was identified with general linear model(GLM)and mixed linear model(MLM)methods that explained 65.5%and 36.1%of the phenotypic variations,***-three SNPs associated with remontancy were detected in GLM whereas no SNP was detected in *** SNP locus(Hy_CAPS_Inflo)was converted to a cleaved amplified polymorphic sequence(CAPS)marker that showed absolute identification accuracy(100%)of inflorescence type in a validation panel consisting of eighteen *** *** SNP was investigated in 341 F1 progenies using genotyping by sequencing(GBS)and co-segregated with inflorescence type(χ^(2)=0.12;P=0.73).The SNP was subsequently used for breeding selection using kompetitive allele specific PCR(KASP)*** directions for the use of genomics and MAS in hydrangea breeding improvement are *** results presented in this study provide insights for further research on understanding genetic mechanisms behind inflorescence type and remontancy in *** CAPS and KASP markers developed here will be immediately useful for applying MAS to accelerate breeding improvement in hydrangea.

关键词： breeding cultivar CAPS

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Counting your sperm before they fertilize： are sperm counts really declining？

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Asian Journal of Andrology 2013年第2期15卷 179-183,I0004,I0005页

作者： alexander w Pastuszak Dolores J Lamb Scott Department of Urology Baylor College of Medicine Houston TX 77030 USA Center for Reproductive Medicine Baylor College of Medicine Houston TX 77030 USA Department of Molecular Cell Biology Baylor College of Medicine Houston TX 77030 USA

Apurported global decline in sperm counts has been a source of controversy since the early 1990s. Numerous studies performed since then, as well as reanalysis of the original data, show either no changes, or even increases, in sperm concentrations over time. In this review, we discuss the 1992 meta-analysis that initiated the continuing debate on whether sperm concentrations are declining, and the com- munity discussion surrounding it over the past two decades. we also highlight studies evaluating sperm concentrations performed since the initial study that produced different results, and conclude that no definitive cause for a decrease in sperm counts has been established, and the effects of geography and environment on sperm counts are unclear.

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Clostridium difficile colitis and zoonotic origins—a narrative review

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Gastroenterology Report 2018年第3期6卷 157-166,I0001页

作者： alexander w.w.Brown Robert B.wilson General Surgery Department Liverpool HospitalElizabeth StLiverpoolNSW 2170Australia

Clostridium difficile is amajor cause of hospital-associated diarrhoea,and in severe cases leads to pseudomembranous colitis and *** frequency of *** infection(CDI)has increased in recent decades,with 453000 cases identified in 2011 in the *** is related to antibiotic-selection pressure,disruption of normal host intestinalmicrobiota and emergence of antibiotic-resistant *** *** burden of community-acquired CDI has been increasingly appreciated,with disease identified in patients previously considered low-risk,such as young women or patients with no prior antibiotic *** has been identified in livestock animals,meat products,seafood and *** has been postulated that the pool of *** in the agricultural industrymay contribute to human *** is widespread environmental dispersal of *** *** households,turf lawns and public spaces are extensively contaminated,providing a potential reservoir for community-acquired *** Australia,this is particularly associated with porcine-derived *** UK PCR ribotype 014/*** this article,the epidemiological differences between hospital-and community-acquired CDI are discussed,including some emerging evidence for community-acquired CDI being a possible zoonosis.

关键词： Clostridium difficile healthcare-associated infections zoonoses

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Varicocele management in the era of in vitro fertilization/intracytoplasmic sperm injection

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Asian Journal of Andrology 2016年第3期18卷 343-348,I0006,I0007页

作者： Piyush Pathak Aravind Chandrashekar Tariq S Hakky alexander w Pastuszak Scott Department of Urology Baylor College of Medicine Houston TX USA Scott Department of Urology Kaiser Permanente Riverside Medical Center Riverside CAUSA Advanced Uro ogy At anta GA USA Scott Department of Urology Center for Reproductive Medicine Baylor College of Medicine Houston TX USA Scott Department of Urology Baylor College of Medicine Houston TxUSA.

Varicocele is the most common surgically treatable cause of male infertility, and often results in alterations in semen parameters, sperm DNA damage, and changes to the seminal milieu. Varicocele repair can result in improvement in these parameters in the majority of men with clinical varicocele; data supporting repair in men with subclinical varicocele are less definitive. In couples seeking fertility using assisted reproductive technologies （ARTs）, varicocele repair may offer improvement in semen parameters and sperm health that can increase the likelihood of successful fertilization using techniques such as in vitro fertilization （IVF） or intracytoplasmic sperm injection （ICSI）, or may decrease the level of ART needed to achieve successful pregnancy. Male infertility is an indicator of general male health, and evaluation of the infertile male with an eye toward future health can facilitate optimal screening and treatment of these men. Furthermore, varicocele may represent a progressive lesion, offering an argument for its repair, although this is currently unclear.

关键词： hypogonadism Leydig cell male fertility Sertoli cell varicocele

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The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

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Asian Journal of Andrology 2013年第3期15卷 301-308页

作者： alexander w wyatt Fan Mo Yuzhuo wang Colin C Collins Vancouver Prostate Centre & Department of Urologic Sciences University of British Columbia Vancouver BC V6H 3Z6 Canada Department of Experimental Therapeutics BC Cancer Agency Vancouver BC VSZ 1L3 Canada

Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer ＇omics＇, including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

关键词： cancer sequencing copy number fusion gene genome genome rearrangement personalized oncology prostate cancer transcriptome

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Phase field modeling with large driving forces

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npj Computational Materials 2023年第1期9卷 623-631页

作者： Jin Zhang alexander F.Chadwick David L.Chopp Peter w.Voorhees Department of Materials Science and Engineering Northwestern UniversityEvanstonIL 60208USA Department of Engineering Sciences and Applied Mathematics Northwestern UniversityEvanstonIL 60208USA

There is growing interest in applying phase field methods as quantitative tools in materials discovery and ***,large driving forces,common in many materials systems,lead to unstable phase field profiles,thus requiring fine spatial and temporal *** demands more computational resources,limits the ability to simulate systems with a suitable size,and deteriorates the capability of quantitative ***,we develop a strategy to map the driving force to a constant perpendicular to the *** with the third-order interpolation function,we find a stable phase field profile that is independent of the magnitude of the driving *** power of this approach is illustrated using three *** demonstrate that by using the driving force extension method,it is possible to employ a grid size orders of magnitude larger than traditional *** approach is general and should apply to many other phase field models.

关键词： forces interpolation apply

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